The present invention relates generally to methods and apparatus for rapidly screening an array of diverse materials that have been created, for example, on a single substrate surface. More specifically, the invention is directed to optical techniques for screening libraries of different materials.
Combinatorial synthesis is the approach of creating extensive libraries of diverse samples by combining a set of components in many possible ways. The approach has been very successfully demonstrated for chemical compounds. Many classes of libraries can be generated combinatorially including inorganics, intermetallics, metal alloys and ceramics. Various surface deposition techniques, masking techniques and processing conditions allow a few to hundreds of thousands of materials with distinct compositions to be generated per square inch. Fields where combinatorial synthesis is important include pharmaceuticals, electrical engineering, chemistry, materials science, earth science, engineering and other related fields.
Techniques known in the art for rapid screening of libraries of diverse materials include: detecting changes in polarization associated with orientational order, dielectric coefficient, or magnetization; infrared imaging to identify active catalysts; photon scattering for the analysis of molecular weight and gas chromatography/mass spectroscopy (GC/MS). Gas chromatography and high-throughput detection are employed to identify and characterize gas phase products or volatile components, and mass spectroscopy is a method in analytical chemistry for the identification of chemical species. U.S. Pat. No. 6,034,775, which is hereby incorporated herein by reference in its entirety, gives an overview of synthesis techniques and optical screening techniques.
While the above techniques are useful, there are few, if any, techniques for rapid screening of libraries for characteristics such as crystalline phase or elemental composition, and which are easily identified with x-ray analysis. In addition, many of the optical techniques described above are destructive. For example, members of a library may be heated and measurements performed on what volatizes off of the members. Thus, it is desirable to have techniques for rapid large scale screening of combinatorial libraries using x-ray analytical techniques. X-rays provide information that other techniques do not and x-ray analysis is non-destructive allowing the libraries to be referred to and tested more than once.
Typically, when an interesting chemical combination is found in a combinatorial library, bulk samples of the compound are made for x-ray analysis. This process is both time consuming and limited because members of the library may be overlooked. In addition, the X-ray sources used in the evaluation of bulk samples are large high power sealed tubes (xcx9cfew kilowatts) or rotating anode sources. These sources are large, require water cooling and high voltage and are very expensive. Thus, there is a need for x-ray analysis of a combinatorial library directly using low power (approximately less than a few hundred watts) X-ray laboratory sources to increase efficiency, reduce measurement time, and increase thoroughness of evaluation.
Currently, in limited cases combinatorial libraries have been analyzed using synchrotron x-ray sources. While synchrotron radiation has some distinct advantages, there are a number of drawbacks. Access to synchrotron sources is limited and expensive. The cost of a synchrotron facility is on the order of $100M. Synchrotron facilities are typically research facilities and are not designed for large scale screening of libraries. Combinatorial screening involves the high-throughput analysis of a large number of samples, typically 1000-100,000. Synchrotron facilities have a wide range of users and thus are designed for a wide range of experiments. Thus, access to a synchrotron for large scale screening of libraries is not practical.
It is highly desirable to do the x-ray screening in parallel with the processing of the libraries. This would require having deposition or processing equipment on site at a synchrotron facility. This is also not very feasible. Unlimited access to single or multiple laboratory x-ray sources combined with appropriate x-ray optics clearly has a distinct advantage due to their cost (i.e., a greater than 3 orders of magnitude reduction in instrument cost compared to a synchrotron facility), availability, and scalability. The use of synchrotrons, despite the difficulty, demonstrates the importance of X-ray analysis in evaluation of combinatorial libraries.
As noted, x-ray analysis on libraries has been performed using synchrotron x-ray beams. The power in an x-ray beam from a synchrotron (approximately 1011 photons/sec in a 1 mm spot) is at least three or more orders of magnitude larger than the power provided by a laboratory x-ray source (approximately 107 photons/sec in a 1 mm spot). However, by coupling an appropriate x-ray optic to the laboratory source as proposed herein, adequate intensities (approximately 108 photons/sec in a 100 xcexcm spot) can be achieved to perform rapid screening on combinatorial libraries.
In this disclosure, a device is described for the controlled use of x-ray beams. Uses of x-ray beams include x-ray synthesis techniques, x-ray sensitive protecting groups, radiation damage effects for evaluation, and screening of libraries of different materials.
In one aspect of the invention, a laboratory based x-ray system is described that provides adequate power in a monochromatic or polychromatic focused or collimated beam. This device includes an x-ray laboratory source, x-ray optic and a detector for determining the structure, composition and/or valence state of any member of the library.
In another aspect, apparatus for characterizing materials are presented which include a laboratory x-ray source for emitting x-rays, and a combinatorial library. The combinatorial library is disposed so that at least a portion of the emitted x-rays impinge upon at least part of the library. A detector and an x-ray optic are also provided. The detector comprises one of an x-ray detector or an electron energy detector, and is disposed to detect x-rays or electron energy after the emitted x-ray has impinged upon the combinatorial library. The x-ray optic can be disposed between the laboratory x-ray source and the combinatorial library for capturing emitted x-rays from the laboratory x-ray source and directing the emitted x-rays to impinge upon the combinatorial library, or between the combinatorial library and the detector for capturing x-rays after impinging upon the combinatorial library and directing the x-rays to the detector. The x-ray optic can comprise a polycapillary optic, a multilayer optic, a singly curved crystal, a doubly curved crystal or a grazing incidence single reflection optic, etc.
Methods for characterizing materials of a combinatorial library are also described and claimed herein.
Additional features and advantages are realized through the techniques of the present invention. Other embodiments and aspects of the invention are described in detail herein and are considered part of the claimed invention.